Magnetic resonance imaging of metastatic disease to the brain with gadobenate dimeglumine.

Seventy-four patients with one to eight proven intraaxial brain metastases received a total cumulative dose of 0.2 mmol/kg bodyweight gadobenate dimeglumine, administered as sequential injections of 0.05, 0.05 and 0.1 m mol/kg over a 20-min period. MR imaging was performed before the first administration (T2- and T1-weighted sequences) and after each injection of contrast agent (T1-weighted sequences only). Quantitative assessment of images revealed significant (P <0.01) dose-related increases in lesion-to-brain (L/B) ratio and percent enhancement of lesion signal intensity. Qualitative assessment by two independent, blinded assessors revealed additional lesions in 22%, 25% and 38% (assessor 1) and 29%, 32% and 34% (assessor 2) of patients after each cumulative dose when compared with combined T1- and T2-weighted pre-contrast images. Significantly more lesions (P < 0.01) were noted by both assessors after the first injection and by one assessor after each subsequent injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted in 12%, 16% and 28% of patients by assessor 1 following each dose and in 24%, 27% and 30% of patients by assessor 2. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced MRI. For patients with one lesion observed after an initial dose of 0.05 mmol/kg, additional lesions were noted by assessors 1 and 2 in 9.1% and 11.8% of patients, respectively, after a cumulative dose of 0.1 mmol/kg and in a further 9.1% and 5.9% of patients, respectively, after a cumulative dose of 0.2 mmol/kg. No safety concerns were apparent.

Gadobenate dimeglumine-enhanced magnetic resonance imaging of intracranial metastases: effect of dose on lesion detection and delineation.

Seventy-four patients with one to eight proven intraaxial metastatic lesions to the brain received a total gadobenate dimeglumine dose of 0.3 mmol/kg of body weight, administered as three sequential bolus injections of 0.1 mmol/kg, at 10-minute intervals over a 20-minute period. Quantitative and qualitative assessments of efficacy were performed after each injection and a full evaluation of safety was conducted. Cumulative dosing produced significant (P < 0.01) dose-related increases in lesion-to-brain (L/B) ratio and lesion signal intensity (SI) enhancement. Two independent, blinded assessors noted additional lesions, compared to unenhanced images in 31% and 33%, 49% and 42%, and 50% and 48% of patients after each cumulative dose, respectively. Significantly more lesions were noted after the first injection, compared to unenhanced images (P = 0.002 and P < 0.001; assessors 1 and 2, respectively), and after a second injection, compared to the first (P < 0.001 and P = 0.039; assessors 1 and 2, respectively). Neither assessor noted significantly more lesions after the third injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted by assessors 1 and 2 for 27% and 26%, 48% and 35%, and 42% and 41% of patients, respectively, following each injection. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced magnetic resonance imaging (MRI). For patients with one lesion observed after 0.1 mmol/kg of gadobenate dimeglumine, additional lesions were noted for 24% and 17% of patients (assessors 1 and 2, respectively) following a second 0.1 mmol/kg injection. Only assessor 2 noted additional lesions following the third 0.1 mmol/kg injection. The findings of on-site investigators concurred with those of the two off-site assessors. No safety concerns were apparent.

Detection of intracranial metastases: a multicenter, intrapatient comparison of gadobenate dimeglumine-enhanced MRI with routinely used contrast agents at equal dosage.

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (MultiHance) with other commercially available MRI contrast agents for the detection of intracranial metastases. METHODS: A retrospective assessment was performed on MR images from 22 patients enrolled in a prior phase II clinical trial of gadobenate dimeglumine. Each patient underwent two examinations: a first examination with one of three "comparator" agents (gadopentetate dimeglumine, gadodiamide, and gadoterate meglumine) at a dosage of either 0.1 or 0.2 mmol/kg, and then a similar examination with gadobenate dimeglumine at equal dosage. All images were evaluated randomly for lesion number and location in unpaired and then paired fashion by two independent, masked neuroradiologists. A third assessor performed quantitative assessments on the available complete sets of digitally recorded images (10 cases). RESULTS: The findings for the comparator agents were pooled. Sensitivity for lesion detection with gadobenate dimeglumine (93%-100%) was markedly superior to that of comparator-enhanced examinations (65%-73%). The increase of lesion-to-brain contrast of the main lesion was consistently greater with gadobenate dimeglumine than with comparator agents relative to unenhanced contrast (+43% vs. +27%). CONCLUSIONS: Gadobenate dimeglumine proved to be a more efficacious agent than comparator contrast agents for the detection of intracranial metastatic lesions: superior efficacy was noted by both reviewers for total lesion count as well as for sensitivity and positive predictive value for lesion detection. The higher relaxivity of gadobenate dimeglumine might explain the superior sensitivity of gadobenate dimeglumine-enhanced MRI for the detection of central nervous system metastases.

Dysembryoplastic neuroepithelial micro-tumor in a 75-year-old patient with long-standing epilepsy.

Dysembryoplastic neuroepithelial tumors (DNT) are rare, cortically located neoplasma associated with intractable partial complex seizures. This entity was first described by Daumas-Duport et al. [1988], who also coined the term DNT. In that report, at the time of operation, the patients' ages ranged from 3 to 30 years and the duration of symptoms ranged from 2 to 18 years. In contrast, we observed a histologically comparable tumor in a 75-year-old female with a 60 year epilepsy history. Autopsy revealed an 8 mm large tumor in the right hippocampus. In view of the extremely prolonged course of the patient's symptoms and the complete lack of excessive cell proliferation, the differentiation of a genuine tumor versus a hamartoma remains equivocal.

Dynamics of tracer distribution in radiation induced brain oedema in rats.

The dynamic behaviour of the distribution of Evans blue (EB), sodium fluorescein (SF), Lucifer yellow (LY) and horseradish peroxidase (HRP) was studied using standard light- and fluorescence microscopy following ultraviolet radiation induced brain oedema in the rat model. The cerebral cortex was irradiated after craniotomy (2 x 2 mm) under anaesthesia. The tracers were injected (iv) 30 min prior to radiation. Animals were perfused with glutaraldehyde through the heart at different survival periods ranging from 30 min to 24 h post irradiation. The results showed a remarkable difference in distribution and spread of these tracers in the oedematous brain following radiation. The extravasation of EB was evident in ipsilateral cortex 6 h after radiation which extended to the contralateral side at the end of the 24 h survival period. The HRP reaction product was seen in the necrotic area 3 h after radiation which further extended to the underlying white matter at 24 h survival. The LY stained the ipsilateral micronecrotic area 6 h after radiation, whereas a non-specific diffuse fluorescence of SF was noted at this time period. These results point out a specific selectivity of tracer distribution in oedematous brain following ultraviolet radiation.

[Experimental thrombolysis of thromboembolisms in the middle cerebral artery circulatory area]. / Experimentelle Thrombolyse von Thrombembolien im Arteria-cerebri-media-Stromgebiet.

Since the majority of ischaemic cerebral infarcts is caused by thromboemboli, we determined the benefit of fibrinolytic therapy in acute stroke. Thromboemboli were induced in the middle cerebral artery of 21 dogs. Urokinase was started at different time intervals after infarction (1, 3 and 5 hours) at a rate of 1000 IU/kg/min. Angiographically controlled thrombolysis was achieved in all 15 treated cases, whereas in the control group (n = 6) no case of recanalisation was observed. Systemic fibrinolysis occurred in all cases. Postmortem examinations of the brains showed no intracerebral haemorrhages. Our findings indicate that urokinase treatment may be of value in acute ischaemic stroke.

[Thrombolysis of cerebral thromboembolism by urokinase in an animal model]. / Untersuchungen zur Thrombolyse zerebraler Thrombembolien mittels Urokinase an einem Tiermodell.

The majority of ischemic cerebral insults are caused by thromboembolism. In animal experiments we have investigated the possibility of reperfusing ischemically damaged brain tissue by thrombolysis of cerebral emboli. 1, 3 and 5 hours after cerebral infarction due to thromboembolism, thrombolytic treatment with urokinase (1000 IU/kg/min) was started. Thrombolysis, monitored by angiography, was successful in all cases (n = 15). In all cases the fall in fibrinogen, alpha 2-antiplasmin and plasminogen reflected systemic fibrinolytic effects. Anatomo-pathologic investigation of the brains revealed no intracerebral bleeding complications. The results of the study suggest a favourable effect of urokinase on acute ischemic cerebral infarction.